Low dose IFN-gamma compositions and their use for treatment of interferon-sensitive diseases

Abstract

The use of low doses of IFN-gamma in the treatment of interferon-sensitive diseases is described. The IFN-gamma can be administered orally, preferably buccally or sublingually, or parenterally in low doses to activate monocyte, neutrophil, or B cell function, to decrease acute inflammation, or to treat cancer, bacterial or fungal diseases, or fibrosis in a patient suffering from such disease states. Pharmaceutical formulations containing low doses of IFN-gamma in combination with a pharmaceutical acceptable carrier and suitable for oral administration are also described.

What is claimed is:  
     
         1 . A method for reducing acute inflammation in a warm-blooded vertebrate suffering from such inflammation, said method comprising the steps of administering orally or parenterally to said vertebrate about 0.1 to about 10,000 IU of IFN-gamma/kg of body weight of said vertebrate and reducing said acute inflammation.  
     
     
         2 . The method of  claim 1  wherein the IFN-gamma is administered buccally or sublingually in a solution or in a solid saliva-soluble dosage form.  
     
     
         3 . The method of  claim 1  wherein the vertebrate is a human patient suffering from an inflammation induced by radiation of the lungs, brain or kidney during radiation therapy for tumors.  
     
     
         4 . The method of  claim 1  wherein the acute inflammation is the result of reperfusion injury incident to stroke or coronary artery blockage.  
     
     
         5 . The method of  claim 1  wherein the warm-blooded vertebrate is a human patient suffering from a traumatic injury to the brain or spinal cord.  
     
     
         6 . The method of  claim 1  wherein the acute inflammation is the result of traumatic bums in a human patient.  
     
     
         7 . The method of  claim 1  wherein the acute inflammation is asthma.  
     
     
         8 . The method of  claim 1  wherein the interferon-gamma is administered at about 1 to about 500 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         9 . The method of  claim 1  wherein the interferon-gamma is administered at about 1 to about 100 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         10 . A method for treating or preventing IFN-gamma sensitive disease states selected from the group consisting of diseases characterized by monocyte and neutrophil dysfunction, cancer and fibrosis in a human patient suffering from such disease, said method comprising the steps of administering orally or parenterally to said patient about 0.1 to about 10,000 IU of IFN-gamma/kg of body weight of said vertebrate, and treating or preventing said disease states.  
     
     
         11 . The method of  claim 10  wherein the disease state is selected from the group consisting of chronic granulomatosis disease and osteopetrosis.  
     
     
         12 . The method of  claim 10  wherein the disease state is fibrosis of any organ.  
     
     
         13 . The method of  claim 10  wherein the interferon-gamma is administered at about 1 to about 500 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         14 . The method of  claim 10  wherein the interferon-gamma is administered at about 1 to about 100 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         15 . A method for treating or preventing bacterial or fungal disease in a warm-blooded vertebrate susceptible to said diseases comprising the steps of administering orally or parenterally to said vertebrate about 0.1 to about 10,000 IU of IFN-gamma/kg of body weight of said vertebrate and treating or preventing said bacterial or fungal disease.  
     
     
         16 . The method of  claim 15  wherein the IFN-gamma is administered into the oral cavity.  
     
     
         17 . The method of  claim 16  wherein the IFN-gamma is administered sublingually or buccally.  
     
     
         18 . The method of  claim 15  wherein the IFN-gamma is administered in a liquid dosage form.  
     
     
         19 . The method of  claim 15  wherein the IFN-gamma is administered in a solid dosage form.  
     
     
         20 . The method of  claim 19  wherein the solid dosage form is saliva-soluble and prepared for dissolution in saliva in the mouth.  
     
     
         21 . The method of  claim 15  wherein the interferon-gamma is administered at about 0.1 to about 5000 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         22 . The method of  claim 15  wherein the interferon-gamma is administered at about 1 to about 500 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         23 . The method of  claim 15  wherein the interferon-gamma is administered at about 1 to about 100 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         24 . A pharmaceutical formulation for treatment of a disease selected from the group consisting of acute inflammation, monocyte, neutrophil, or B cell dysfunction, cancer, bacterial and fungal diseases, and fibrosis, said formulation comprising in unit dosage form about 10 to about 50,000 IU of human IFN-gamma and a pharmaceutically acceptable carrier therefor.  
     
     
         25 . The pharmaceutical formulation of  claim 24  in liquid form.  
     
     
         26 . The pharmaceutical formulation of  claim 24  in solid form.  
     
     
         27 . The pharmaceutical formulation of  claim 24  wherein the pharmaceutical acceptable carrier comprises a saliva-soluble solid and the formulation is in lozenge dosage form.  
     
     
         28 . A pharmaceutical formulation for treatment of a disease selected from the group consisting of acute inflammation, monocyte, neutrophil, or B cell dysfunction, cancer, bacterial and fungal diseases, and fibrosis, said formulation comprising in unit dosage form about 10 to about 50,000 IU of human IFN-gamma, a therapeutic agent selected from the group consisting of an antibiotic, an antifungal, an antifibrotic, and a chemotherapeutic agent known for use in cancer therapy or for treatment of immune diseases characterized by hypoactive or hyperactive immune system dysfunction, and a pharmaceutically acceptable carrier therefor.  
     
     
         29 . A method of activating the B-cell population of a patient suffering from a disease state characterized by attenuated B-cell function said method comprising the steps of administering orally or parenterally to said patient about 0.1 to about 10,000 IU of IFN-gamma/kg of body weight of said vertebrate and activating at least a portion of said B-cell population.  
     
     
         30 . The method of  claim 29  wherein the IFN-gamma is administered into the oral cavity.  
     
     
         31 . The method of  claim 30  wherein the IFN-gamma is administered sublingually or buccally.  
     
     
         32 . The method of  claim 29  wherein the IFN-gamma is administered in a liquid dosage form.  
     
     
         33 . The method of  claim 29  wherein the IFN-gamma is administered in a solid dosage form.  
     
     
         34 . The method of  claim 33  wherein the solid dosage form is saliva-soluble and is in lozenge dosage form.  
     
     
         35 . The method of  claim 29  wherein the interferon-gamma is administered at about 0.1 to about 5000 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         36 . The method of  claim 29  wherein the interferon-gamma is administered at about 1 to about 500 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         37 . The method of  claim 29  wherein the interferon-gamma is administered at about 1 to about 100 IU of interferon-gamma/kg of body weight of said vertebrate.  
     
     
         38 . A method for treating or preventing bacterial or fungal disease in a warm-blooded vertebrate susceptible to said diseases, the method comprising the steps of administering orally or parenterally to said vertebrate about 0.1 to about 10,000 IU of IFN-gamma/kg of body weight of said vertebrate and a therapeutic agent selected from the group consisting of an antibiotic and an antifungal, and treating or preventing said bacterial or fungal disease.  
     
     
         40 . A method for treating or preventing IFN-gamma sensitive disease states selected from the group consisting of diseases characterized by monocyte and neutrophil dysfunction, cancer and fibrosis in a human patient suffering from such disease, said method comprising the steps of administering orally or parenterally to said patient about 0.1 to about 10,000 IU of IFN-gamma/kg of body weight of said vertebrate and a therapeutic agent selected from the group consisting of an antifibrotic and a chemotherapeutic agent known for use in cancer therapy or for treatment of immune diseases characterized by hypoactive or hyperactive immune system dysfunction, and treating or preventing said disease states.